We plan to explore whether the highly successful attenuated yellow fever (YF-17D) vaccine, rDNA delivered by electroporation along with IL-12 and rAd35 can be used as vectors to express SIV proteins in a prime/boost regimen for vaccination against the AIDS virus. In a highly integrated series of experiments, we will first define the best viral targets for a vaccine. We will then bring the results together in a final efficacy experiment to test the vectors that, if successful, could prevent suffering by millions of people worldwide. Our application seeks to address four of the ten research areas outlined in the HIVRAD program announcement. Our project has the potential to impact HIV vaccine development on two fronts. First, we will define the targets of a successful vaccine in a challenge experiment. This will allow us to design a vaccine encoding the critical targets of a successful immune response. Second, we will develop three entirely novel vaccine vectors. If we are successful in this endeavor, our results will have a profound effect on HIV vaccine design.